Methods and compositions for the treatment of diverticulosis

ABSTRACT

The present invention is directed to methods and compositions for the treatment of diverticulosis. It is more specifically directed to compositions including L-glutamine, its salts, or its derivatives, and uses of such compositions in the treatment of diverticulosis. In a method aspect, the present invention provides a method of treating diverticulosis. The method includes ingestion of 0.05 g/kg body weight to 10.0 g/kg body weight of L-glutamine, an L-glutamine salt or an L-glutamine derivative per day by a person who has diverticulosis.

This application claims priority benefit of U.S. Provisional PatentApplication No. 61/630,831, filed Dec. 19, 2011. The entire content ofthat application is hereby incorporated by reference herein in itsentirety.

FIELD OF THE INVENTION

The present invention is directed to methods and compositions for thetreatment of diverticulosis. It is more specifically directed tocompositions including L-glutamine, its salts, or its derivatives, anduses of such compositions in the treatment of diverticulosis.

BACKGROUND OF THE INVENTION

Diverticulosis refers to a condition where pouches (i.e., diverticula)form along the colon wall. The pouches are typically 5 to 10 millimetersin diameter and are formed in approximately 50 percent of individuals 60years old or older.

The etiology of diverticulosis is not well understood. Current theoryfocuses on observed nutritional differences between cultures: Thosecultures that eat a high fiber diet (e.g., Asia and Africa) have a verylow incidence of diverticulosis; those that eat a low fiber diet (e.g.,United States and Europe) have a high incidence of diverticulosis.Certain physicians believe that the colon of a person eating a diet lowin fiber must exert more pressure than usual to move waste through hiscolon. The relative high pressure distorts weak spots in the colon whereblood vessels pass through the muscle layer of the bowel wall, therebyforming pouches.

Many cases of diverticulosis go undiscovered, because the conditionalone does not cause symptoms. Diverticulosis is typically diagnosedafter a patient experiences complications, such painful diverticulardisease or diverticulitis. In other cases, it is discovered during ascreening examination (e.g., colonoscopy).

Diverticulosis is usually treated using a combination of nutritionalguidelines and medication. A patient may follow a diet regimen involvingingestion of high fiber foods with the objective of consuming 30 to 35grams of fiber per day. Antispasmodic drugs may be prescribed to relaxmuscles around the digestive tract. Painkillers may be administeredwhere diverticulitis or other complications of diverticulosis haveoccurred.

There is a need in the art for additional compositions and methods thatcan be used to treat diverticulosis. That is an object of the presentinvention.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows L-glutamine (1) and L-glutamine salts and derivatives (2).

SUMMARY OF THE INVENTION

The present invention is directed to methods and compositions for thetreatment of diverticulosis. It is more specifically directed tocompositions including L-glutamine, its salts, or its derivatives, anduses of such compositions in the treatment of diverticulosis.

In a method aspect, the present invention provides a method of treatingdiverticulosis. The method includes ingestion of 0.05 g/kg body weightto 10.0 g/kg body weight of L-glutamine, an L-glutamine salt or anL-glutamine derivative per day by a person who has diverticulosis.

In a composition aspect, the present invention provides acomposition fortreating diverticulosis. The composition includes L-glutamine, anL-glutamine salt or an L-glutamine derivative and a fiber supplement.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to methods and compositions for thetreatment of diverticulosis. It is more specifically directed tocompositions including L-glutamine, its salts, or its derivatives, anduses of such compositions in the treatment of diverticulosis.

The structure of L-glutamine is shown in FIG. 1, compound 1. L-glutaminesalts and derivatives are shown as compound 2 in FIG. 1. NonlimitingL-glutamine salts and derivatives have the following substituents inreference to compound 2:

R₁ is NH₂;

R₂ is NH₂, NH₃ ⁺, NH₃Br, NH₃OPO₃H, NH₃OC(O)CH₃ (i.e., acetate salt),NH₃OC(O)CHCHCO₂H (i.e., fumarate salt—trans olefin),NH₃OC(O)CH(OH)CH(OH)CO₂H (i.e., tartrate salt), NH₃OC(O)CHCHCO₂H (i.e.,maleate salt—cis olefin), NH₃OC(O)CH₂—C(OH)(CO₂H)CH₂CO₂H (i.e., citratesalt), NH₃OC(O)CO₂H (i.e., oxalate salt), NH₃OS(O)₂OH (i.e.,methanesulfonate salt), NH₃OS(O)₂C₆H₄CH₃ (i.e., p-toluenesulfonatesalt), and, NH₃OC(O)C(O)CH₂CH₂CO₂H (i.e., alpha-ketoglutarate salt).

R₃ is OH, O⁻, ONa, OK, OCa, OLi, ONH₂(CH₂C₆H₅)CH₂CH₂NHCH₂C₆H₆ (i.e.,benzathine salt), ON(CH₂CH₃)₂CH₂CH₂OC(O)C₆H₃ClNH₂ (i.e., chloroprocainesalt), ON(CH₃)₃CH₂CH₂OH (i.e., choline salt), ONH₂(CH₂CH₂OH)₂ (i.e.,diethanolamine salt), ONH₃CH₂CH₂OH (i.e., ethanolamine salt),ONH₃CH₂CH₂NH₂ (i.e., ethyldiamine salt),ONH₂(CH₃)CH₂CH(OH)CH(OH)CH(OH)CH(OH)CH₂OH (i.e., meglumine salt),ONH₃C(CH₂OH)₃ (i.e., tromethamine salt), ONH₃C(CH₃)₃ (i.e.,tertiary-butylamine salt), ON(CH₂CH₃)₂CH₂CH₂OC(O)C₆H₄NH₂ (i.e., procainesalt), NHCH(CH₃)CO₂H, NHCH(CH(CH₃)₂)CO₂H, NHCH(CH(CH₃)(CH₂CH₃))CO₂H,NHCH(CH₂CH(CH₃)₂)CO₂H, NHCH(CH₂CH₂SCH₃)CO₂H, NHCH(CH₂C₆H₅)CO₂H,NHCH(CH₂C₆H₅OH)CO₂H, NHCH(CH₂C₈H₆N)CO₂H, NHCH₂CO₂H,NHCH(CH₂CH₂C(O)NH₂)CO₂H, NHCH(CH₂C(O)NH₂)CO₂H, NHCH(CH(OH)CH₃)CO₂H,NHCH(CH₂OH)CO₂H, NHCH(CH₂CH₂CO₂H)CO₂H, NHCH(CH₂CO₂H)CO₂H.

Typically, a single compound (e.g., L-glutamine) is administered to aperson seeking treatment for diverticulosis. In certain cases, however,a mixture of two or more compounds may be administered. For instance,L-glutamine may be administered with one or more L-glutamine salts orderivatives.

L-glutamine, its salts, derivatives or mixtures may be administered inany suitable way. For example, in certain cases it is administered as anaqueous solution. The solution may only have L-glutamine, salts orderivatives as dissolved ingredients, or it may include otherpharmaceutically acceptable compounds. Nonlimiting examples of suchcompounds include buffers and flavorants.

Other, non-limiting examples of ways in which L-glutamine, its salts,derivatives or mixtures may be administered include: as a suspension ina liquid (e.g., water or juice); as a solid, either as a powder or inanother form (e.g., pill or capsule); as a mixture with food (e.g.,yogurt). As with the aqueous solution, the preceding administrationforms may include other pharmaceutically acceptable ingredients.

The amount of L-glutamine, salts or derivatives administered accordingto the present invention typically range from 0.05 g/kg body weight to10.0 g/kg body weight. Oftentimes, the amount ranges from 0.10 g/kg bodyweight to 8.0 g/kg body weight. In certain cases, the amount ranges from0.15 g/kg body weight to 7.0 g/kg body weight.

L-glutamine, its salts or derivatives are typically administered to aperson once per day. The compounds may, however, be administered morethan once per day where indicated.

Where compositions of the present invention are used to treatdiverticulosis, they may be combined with other methods used to treatdiverticulosis. For instance, the compositions may be administered aspart of a dietary regimen focused on the inclusion of increased fiber.

Compositions of the present invention may also be administered and/orcombined with a fiber supplement such as CITRUCEL, BENEFIBER andMETAMUCIL. The fiber supplement may include soluble and/or insolublefiber, or the supplement may be entirely composed of soluble and/orinsoluble fiber. Nonlimiting examples of fiber with which thecompositions can be combined include: methylcellulose; wheat dextrinnatural soluble fiber; and, psyllium fiber. The fiber may also includecombinations of the foregoing types of fibers.

Combinations of the compositions and fiber may be of any suitable form.The combination may be, for example, in the form of a powder, a capsule,a caplet, a chewable tablet. It may also be included in other supplementforms, such as drinks or gels.

Compositions according to the present invention may be used to treatdiverticulosis as determined by a number of different methods to imagecolon pouches. Nonlimiting examples of imaging methods include:colonoscopy; computed tomography; and, x-ray based on a barium enema.

After administration of L-glutamine, its salts or derivatives for threemonths, four months, five months, six months, seven months, eightmonths, nine months, ten months, eleven months or twelve months, thenumber of pouches observed in a patient's colon have been reduced by atleast twenty-five (25) percent. In certain cases, the number of poucheshave been reduced by at least fifty (50) percent or seventy-five (75)percent. In other cases, the number of pouches have been reduced by atleast eighty (80) percent, eighty-five (85) percent, ninety (90)percent, or ninety-five (95) percent.

Experimental Results

A person had a number of diverticula as observed by colonoscopy. Theperson ingested 30 g of L-glutamine per day as an aqueous solution.After twelve months of L-glutamine administration, the number ofdiverticula had been reduced by ninety (90) percent.

1. A method of treating diverticulosis, wherein the method comprisesingestion of 0.05 g/kg body weight to 10.0 g/kg body weight ofL-glutamine, an L-glutamine salt or an L-glutamine derivative per day bya person who has diverticulosis.
 2. The method according to claim 1,wherein the compound ingested is L-glutamine.
 3. The method according toclaim 2, wherein the L-glutamine is ingested as part of an aqueoussolution or suspension.
 4. The method according to claim 3, wherein theL-glutamine is ingested for a period of at least six months.
 5. Themethod according to claim 4, wherein the number of diverticula in theperson with diverticulosis is reduced by at least fifty percent.
 6. Acomposition for treating diverticulosis, wherein the compositioncomprises L-glutamine, an L-glutamine salt or an L-glutamine derivativeand a fiber supplement.
 7. The composition according to claim 6, whereinthe composition comprises L-glutamine.
 8. The composition according toclaim 7, wherein the fiber is selected from a group of fibers consistingof methylcellulose, wheat dextrin and psyllium.
 9. The compositionaccording to claim 8, wherein the composition further comprises aflavorant.
 10. The composition according to claim 9, wherein it is inthe form of a powder, a capsule, a caplet or a chewable tablet.